Selection for Phase Variation of LOS Biosynthetic Genes Frequently Occurs in Progression of Non-Typeable Haemophilus influenzae Infection from the Nasopharynx to the Middle Ear of Human Patients

Kate L Fox,Michael P Jennings,Yogitha N Srikhanta,Lauren O Bakaletz,John M Atack,Laura A Novotny,Anja Eckert,Riccardo Manganelli

doi:10.1371/journal.pone.0090505

Kate L Fox, Michael P Jennings + Show 6 more

Open Access

https://doi.org/10.1371/journal.pone.0090505

Copy DOI

Abstract

Surface structures in Haemophilus influenzae are subject to rapid ON/OFF switching of expression, a process termed phase variation. We analyse tetranucleotide repeats controlling phase variation in lipo-oligosaccharide (LOS) genes of H. influenzae in paired isolates from both the nasopharynx and middle ears of paediatric patients with chronic or recurrent otitis media. A change in expression of at least one of the seven phase variable LOS biosynthesis genes was seen in 12 of the 21 strain pairs. Several strains showed switching of expression in multiple LOS genes, consistent with a key role for phase variable LOS biosynthetic genes in human infection.

Highlights

Non-typeable Haemophilus influenzae (NTHi) strains cause otitis media (OM), sinusitis, conjunctivitis, and acute lower respiratory tract infections
In H. influenzae, phase variation is commonly mediated by mutations in simple tandem DNA repeats that occur in genes, mainly encoding surface expressed virulence determinants [3]
We report an analysis of the phase variation of seven LOS biosynthetic genes in a collection of paired clinical isolates from the nasopharynx and middle ear of paediatric patients with chronic or recurrent OM, in order to look for evidence of selection for LOS phase variants that might have emerged during the transition from nasopharyngeal colonisation to overt infection of the middle ear

Summary

Introduction

Non-typeable Haemophilus influenzae (NTHi) strains cause otitis media (OM), sinusitis, conjunctivitis, and acute lower respiratory tract infections. We report an analysis of the phase variation of seven LOS biosynthetic genes in a collection of paired clinical isolates from the nasopharynx and middle ear of paediatric patients with chronic or recurrent OM, in order to look for evidence of selection for LOS phase variants that might have emerged during the transition from nasopharyngeal colonisation to overt infection of the middle ear.

Results

Conclusion